Treatment Of Cervical Intraepithelial Neoplasia Research Articles

Comparative Study of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy and the Loop Electrosurgical Excision Procedure for the Treatment of Cervical High-Grade Squamous Intraepithelial Lesions.

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24-51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL.

Prognostic outcome of cervical laser ablation using a holmium yttrium-aluminum-garnet (Ho:YAG) laser for the treatment of cervical intraepithelial neoplasia: A single-center retrospective study

ObjectiveAlthough cervical conization is considered a standard treatment for cervical intraepithelial neoplasia (CIN) 2/3, laser ablation can compensate for the disadvantages of the former. CO2, semiconductor, and holmium yttrium-aluminum-garnet (Ho:YAG) lasers are applied in ablation, but no previous studies have shown the effectiveness of any of these techniques. Here, we retrospectively analyzed the application of the Ho:YAG laser in our hospital to verify its efficacy, and discussed the methods for optimal recurrence detection. MethodsWe evaluated the recurrence rates of the pathological condition in patients who underwent laser ablation with a Ho:YAG laser for CIN2/3 at our institution from June 2012 to November 2021. We defined the recurrence as histologically confirmed CIN2 or more advanced stage. Age, preoperative diagnosis, human papillomavirus (HPV) genotype, and postoperative high-risk HPV status were recorded to establish their association with recurrence rates. ResultsWe performed surgery in 607 patients and the 2-year recurrence rate after interventions was 5.6%. Five patients were diagnosed with invasive cancer at the time of recurrence. Older age significantly correlated with higher risk of recurrence, but preoperative CIN grade and preoperative HPV 16/18 status did not significantly affect it. The postoperative high-risk HPV test was 100% sensitive for detecting recurrence. ConclusionsLaser ablation with the Ho:YAG laser yields promising results. Together with postinterventional management, high-risk HPV test after laser ablation should be conducted after diagnostic conization.This study received the approval from the Ethics Committee of the NHO Tokyo Medical Center (Ethics Committee approval number: R22-067).

The Impact of Diagnosis of Human Papillomavirus (HPV) Infection and Electrosurgical Excision Procedure (LEEP) for Cervical Intraepithelial Neoplasia 3 (CIN3) on Women's Sexual Lives.

The aim of the study was to assess sexual health in women who underwent Loop Electrosurgical Excisional Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia 3 (CIN 3). One hundred thirty-one women were enrolled, and the Female Sexual Function Index (FSFI) questionnaire was administered before LEEP and 6 months after the procedure. In almost all of the participants, data revealed a statistically significant worsening in sexual quality of life after LEEP. Therefore, clinicians should be aware of these possible negative effects on sexual behavior, and provide women with appropriate, wide-ranging, and detailed counseling. The data obtained in the present study should help to plan appropriate counseling from communicating HPV diagnosis and medical treatment to CIN3 surgical procedure.

Treatment methods for cervical intraepithelial neoplasia in England: A cost-effectiveness analysis.

To compare the cost-effectiveness of different treatments for cervical intraepithelial neoplasia (CIN). A cost-effectiveness analysis based on data available in the literature and expert opinion. England. Women treated for CIN. We developed a decision-analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10-year period. The costs calculated were those incurred by the National Health Service (NHS) of England. Cost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted. For young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost-effective treatment overall at all willingness-to-pay thresholds. For postmenopausal women, LLETZ remained the most cost-effective treatment up to a threshold of £31,500, but laser conisation became the most cost-effective treatment above that threshold. LLETZ is the most cost-effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence.

Diagnosis and Management of Cervical Squamous Intraepithelial Lesions in Pregnancy and Postpartum.

Perinatal care provides important health care opportunities for many individuals at risk for cervical cancer. Pregnancy does not alter cervical cancer screening regimens. ASCCP risk-based management has a colposcopy threshold of a 4% immediate risk of cervical intraepithelial neoplasia (CIN) 3 or cancer, but the actual risk can be considerably higher based on current and past screening results. Improving cervical cancer outcomes with diagnosis during pregnancy rather than postpartum and facilitating further evaluation and treatment postpartum for lesser lesions are the perinatal management goals. Although colposcopy indications are unchanged in pregnancy, some individuals with lower risk of CIN 2-3 and reliable access to postpartum evaluation may defer colposcopy until after delivery. Cervical intraepithelial neoplasia diagnosed in pregnancy tends to be stable, with frequent regression postpartum, though this is not universal. Colposcopic inspection during pregnancy can be challenging. Although biopsies in pregnancy are subjectively associated with increased bleeding, they do not increase complications. Endocervical curettage and expedited treatment are unacceptable. Treatment of CIN 2-3 in pregnancy is not recommended. Excisional biopsies in pregnancy are reserved for suspicion of malignancy that cannot be confirmed by colposcopic biopsy and when excisional biopsy results would alter oncologic or pregnancy care. Surveillance of high-grade lesions in pregnancy uses human papillomavirus-based testing, cytology, and colposcopy, with biopsy of worsening lesions every 12-24 weeks from diagnosis until postpartum evaluation. Mode of delivery does not definitively affect persistence of CIN postpartum. Postpartum care may involve a full colposcopic evaluation or expedited excisional procedure if indicated.

Modulation of sHLA-G, PD-1, and PD-L1 Expression in Cervical Lesions Following Imiquimod Treatment and Its Association with Treatment Success.

(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.

In-Clinic vs. Online Recruitment of Women with a History of Cervical Intraepithelial Neoplasia or Cervical Cancer to a Smoking Cessation Trial: A Post-hoc Comparison of Participant Characteristics, Study Retention, and Cessation Outcomes.

Recruiting special populations to smoking cessation trials is challenging and approaches beyond in-clinic recruitment may be beneficial. This secondary analysis of data from a smoking cessation RCT for individuals with a history of cervical cancer or cervical intraepithelial neoplasia (CIN) explored differences associated with in-clinic vs. online recruitment. Participants were recruited from clinics within a university-based NCI-designated cancer center (n=87) and online nationally via Facebook (n=115). Baseline measures included sociodemographics, smoking history, and cancer or CIN history. Study retention and smoking abstinence were assessed 12 months post-baseline. Group differences in baseline characteristics were evaluated. Retention and abstinence were evaluated while controlling for group differences and predictors. Participants recruited online (vs. in-clinic) had higher educational attainment (p=.01) and health literacy (p=.003). They were more likely to have CIN vs. cancer, to be further from the time of diagnosis, and to have completed active treatment (p values<.001). While controlling for these group differences and independent predictors, retention was higher among participants recruited online (log-likelihood χ2(1)=11.41, p<.001). There were no recruitment differences in self-reported (p=.90) or biochemically confirmed smoking abstinence (p=.18). Compared to individuals recruited in-person, individuals recruited online were more educated, had higher health literacy, and presented with a different clinical profile (i.e., more likely to have CIN vs. cancer and to have completed active treatment). There were few differences in participant characteristics between recruitment approaches, and no differences on any smoking-related variables. Online recruitment has the potential to improve enrollment of cancer survivors to smoking cessation trials. People with a history of CIN or cervical cancer recruited to a smoking cessation RCT online (vs. in-clinic) were more likely to have a diagnosis of CIN vs. cancer and were more educated and health literate. Participants recruited online were more likely to be retained in the study and there were no differences in smoking abstinence rates at 12-months. Incorporating online recruitment increased the reach of tobacco treatment efforts to a larger and more diverse sample. This could reduce the burden of tobacco-related disease, improve CIN and cancer treatment outcomes, and reduce secondary malignancies and morbidity among this underserved group.

Performance of Different Follow-Up Strategies and Genotype-Based Recurrence Risk After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

Our aim was to evaluate the performance of different follow-up strategies after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3, including human papillomavirus (HPV) detection, cytology, or colposcopy, as well as their combinations. Additionally, we compared the influence of the persistence of HPV 16/18 versus that of other high-risk HPV genotypes (HR-HPV) in the recurrence risk. Retrospective register-based study, including women who had an excision of the transformation zone for CIN2 or CIN3 at our institution, between January 2011 and December 2022. The outcome assessed was histopathological recurrence/persistence of CIN2 or worse. Of the 721 women included, 6.8% (49/721) had recurrence/persistence. The sensitivity, specificity, and positive and negative predictive values of the HPV test were 97.4%, 80%, 22.3%, and 99.8%, respectively, whereas for cotesting (HR-HPV and cytology), 86.8%, 90.1%, 34.4%, and 99.1%, respectively. The referral rates for colposcopy were 24.3% and 14.2%, respectively. The sensitivity of colposcopy was low (40.0%).Women who were initially positive for non-16/18 genotypes at baseline who became HPV16/18 positive during follow-up, had a statistically significant increased risk of CIN2 or worse, compared with those who tested positive only for other HR-HPV genotypes during both stages (hazard ratio = 4.98; 95% CI = 1.66-14.91). Human papillomavirus testing is the best strategy for follow-up after treatment of cervical HSIL. The addition of cytology triage decreases by more than 40% the referrals for colposcopy, without significantly missing cases of recurrence/persistence. Human papillomavirus 16/18 in the follow-up, regardless of being previously positive, is associated with higher risk of recurrence/persistence of HSIL.

Topical imiquimod cream for the treatment of cervical intraepithelial neoplasia

Topical imiquimod cream for the treatment of cervical intraepithelial neoplasia

Фототераностика тяжелых дисплазий и преинвазивного рака шейки матки

Due to the high prevalence of pre-cancerous cervical diseases and cervical cancer, the search, pathogenetic reasoning and evaluation of the efficacy of new approaches to the diagnosis and treatment of these pathologies, including those aimed at fertility preservation, are extremely relevant. Objective. To study the clinical efficacy and safety of phototheranostics as a method of diagnosis and treatment of severe dysplasia and pre-invasive cervical cancer. Patients and methods. An open-label, retrospective-prospective, randomized, comparative, clinical trial involving 94 reproductive-aged patients with morphologically confirmed severe cervical intraepithelial neoplasia (CIN) and pre-invasive cervical cancer was conducted. All patients were divided into two groups: group 1 (comparison) included 49 patients who underwent cervical conization with curettage of the remaining cervical canal; group 2 (study) included 45 patients who underwent phototheranostics: photodynamic therapy (PDT) with simultaneous laser-induced fluorescence excitation. Results. After the first course of phototheranostics, most women in the study group had normal cytological results, which were observed 6, 9, and 12 months after treatment. In these periods, all patients who underwent phototheranostics had a normal colposcopic picture, while in the comparison group, some patients showed signs of cervical lesions. Morphological confirmation of the complete therapeutic effect was considered to be elimination of human papillomavirus (HPV) and normalization of the proliferative activity of the epithelial layer (assessed by the levels of Ki-67 and phosphohistone markers) during phototheranostics. Conclusion. The study demonstrated the high clinical efficacy of phototheranostics in the treatment of CIN and pre-invasive cervical cancer: 85–88% of women achieved the desired therapeutic effect after the first session of phototheranostics, and after the second session, all patients in the study group had complete regression of cervical mucosal lesions. In the study group, higher pregnancy rates and favourable outcomes in patients planning pregnancy confirmed that the use of PDT contributes to fertility preservation in women treated for CIN and pre-invasive cervical cancer, which is associated with the preservation of anatomo-functional characteristics of the cervix when using phototheranostics. Key words: PDT, HPV, photodynamic therapy, fluorescence diagnosis, cervical dysplasia, photosensitizers, pre-invasive cervical cancer, phototheranostics, pregnancy after PDT

Adverse Pregnancy Outcomes Following Cryotherapy, Thermal Ablation and Loop Electrosurgical Excision Procedure for Cervical Intraepithelial Neoplasia Treatment: A Pilot Study among Zambian Women

Adverse Pregnancy Outcomes Following Cryotherapy, Thermal Ablation and Loop Electrosurgical Excision Procedure for Cervical Intraepithelial Neoplasia Treatment: A Pilot Study among Zambian Women

Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia.

To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physicians' discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age.

Lugol's Solution Reduces Positive Margins and Residual Disease After the Large Loop Excision of Transformation Zone.

This study aimed to examine whether the intraoperative use of Lugol's solution reduces the proportion of positive resection margins (RMs) using the data of women who underwent large loop excision of the transformation zone (LLETZ). A total of 1,751 consecutive women with cervical intraepithelial neoplasia (CIN) who underwent LLETZ with or without Lugol's solution were retrospectively retrieved from each database of 3 university hospitals in South Korea. Outcomes included positive RMs and residual disease pathologically confirmed within 6 months after LLETZ. Positive RMs were noted in 345 cases (19.7%). Among 1,507 women followed up, residual disease was diagnosed in 100 cases (6.6%) (69/308 cases with positive RMs; 31/1,199 cases with negative RMs). The Lugol's solution group was less likely to have positive RMs (11.8% vs 25.5%, p < .01), to require additional surgical intervention (5.4% vs 10.2%, p < .01), and to have residual disease (4.9% vs 8.0%, p = .02). On multiple logistic regression analysis, Lugol's solution reduced the proportion of positive RMs (adjusted odds ratio [aOR], 0.31). Age (50 years or older; aOR, 1.64), preconization cervical cytology (aOR, 1.53), high-risk human papillomavirus (aOR, 1.75), and CIN 2 or 3 (aOR, 2.65) were independent risk factors for margin positivity ( p < .01 for all except high-risk human papillomavirus of p = .05). Lugol's solution optimizes CIN treatment by reducing the proportion of positive RMs and residual disease after LLETZ.

Genomic Characterization of Low and High Grade Cervical Intraepithelial Neoplasia in Comparison to Cervical Cancer

Screening reduces incidence of cervical cancer (CC) through identification and treatment of cervical intraepithelial neoplasia (CIN). Triage of CIN must balance between overtreatment versus progression as invasive therapies increase the risk of side effects including obstetric complications. The majority of CIN 1-2 lesions regress and a subset of CIN 3 lesions progress, however, due to inability to differentiate lesions likely to progress, the majority of CIN 2-3 lesions are treated with resection. Improved genomic and molecular identifiers of disease represent an urgent unmet clinical need. Using next generation sequencing of a targeted exome panel of 1109 genes (previously validated), we characterized somatic mutations in 36 CIN (14 CIN 1, 11 CIN 2, 11 CIN 3) and 13 CC samples. Sequencing of CIN samples was performed on exfoliated cervical cells. CIN diagnosis and grade was confirmed on biopsy. Mutation profiles between CIN grades and CC were compared to identify genomic patterns that distinguish these groups. Across the 49 samples sequenced, we identified a total of 5142 somatic mutations, including 2178 missense, 2522 synonymous, 171 nonsense, 62 splice site, 135 inframe indels, and 74 frameshift mutations. The mutation frequency was significantly higher in CC vs CIN1-3 (Table), p<0.01 (Wilcoxon signed-rank test). The difference in mutation frequency and type (Table) was not significant between CIN grades 1, 2 and 3 (p = 0.07, Kruskal-Wallis test). Cancer related pathway signatures were analyzed for the percentage of CC vs CIN samples with at least one altered variant as follows: RTK-RAS (92% vs 31%), PI3K (92% vs 17%), NOTCH (100% vs 39%), WNT (85% vs 14%) and cell cycle (53% vs 3%). Ninety percent of CC samples versus only 30% of CINs had nonsynonymous variants in the RTK-RAS and NOTCH pathways as well as the PI3K pathway which is implicated as a late event in cervical carcinogenesis. We observed recurrent missense variants in ABL1, IGF1R, TSC2 in the CIN2, CIN3 and CC samples, particularly in genes that belong to the RTK-RAS, PI3K, NOTCH pathway signatures. Potential driver mutations in EGFR, PIK3CA, ERBB4, MTOR, CSF1R genes were exclusive to CC samples. Our results show that there is a clear distinction of mutational burden and type between cervical cancer and CIN1-3. However, the pathologic grading of CIN is not consistently associated with dynamic changes in overall mutation burden, type, or specific genes with escalating CIN grade. This data supports the hypothesis that late genetic events in CIN accompany a transition to invasive cervical cancer.

Transvaginal small bowel evisceration after cervical loop electrosurgical excision procedure: a case report

Transvaginal small bowel evisceration is a life-threatening condition, which is usually seen in postmenopausal women with a history of gynecological surgery. Cervical loop electrosurgical excision procedure (LEEP) is widely used in the treatment of cervical intraepithelial neoplasia (CIN), and its surgical risk and postoperative complications are relatively low because of the simplicity of the operation. However, improper operation may result in perforation of the uterus, which can cause prolapse of the small bowel into the vagina. We here reported an extremely rare case of a young woman with transvaginal small bowel evisceration after cervical LEEP, achieving a good prognosis after the prolapsed bowel was reduced. The patient underwent cervical LEEP as a treatment for CIN III, but the LEEP resulted in a laceration of about 4.0 cm × 3.5 cm on the peritoneum of the uterovesical peritoneal reflection and a laceration of about 2.0 cm × 1.5 cm on the anterior wall of the cervical canal. Through the two lacerations, the pelvic cavity is connected to the vagina and the small intestine prolapsed into the vagina. Due to aggressive surgical intervention, the patient achieved a favorable prognosis after successfully reducing the prolapsed bowel.

Feasibility of 5-fluorouracil and imiquimod for the topical treatment of cervical intraepithelial neoplasias (CIN) 2/3.

To determine the feasibility (as measured by tolerability and safety) and efficacy of topical 5-fluorouracil (5-FU) and imiquimod for the treatment of cervical intraepithelial neoplasia (CIN) 2/3. This pilot prospective study was conducted in women aged 18-45 years with p16+ CIN 2/3. Participants underwent an 8-week alternating regimen of self-applied 5% 5-FU on weeks 1, 3, 5, and 7 and physician-applied imiquimod on weeks 2, 4, 6, and 8. Adverse events (AEs) were collected by symptom diary and clinical exam. Feasibility was measured by tolerability and safety (AEs) of the study intervention. Tolerability was assessed as the number of participants able to apply 50% or more of the treatment doses. The safety outcome was calculated as the number of participants who experienced "specified AEs" defined as possibly, probably, or definitely related grade 2 or worse AE or grade 1 genital AEs (blisters, ulcerations, or pustules) lasting more than 5 days. The efficacy of the intervention was determined by histology and high-risk human papillomavirus (hrHPV) testing was done after treatment. The median age of the 13 participants was 27 ± 2.9 years. Eleven (84.61%) participants applied 50% or more of the treatment. All participants reported grade 1 AEs; 6 (46.15%) reported grade 2 AEs; and 0 reported grade 3/4 AEs. Three (23.08%) participants had specified AEs. Histologic regression to normal or CIN 1 among those completing 50% or more of the treatment doses was observed in 10 (90.91%) participants, and 7 (63.63%) tested negative for hr-HPV at the end of the study. Topical treatment for CIN 2/3 with 5-FU/imiquimod is feasible, with preliminary evidence of efficacy. Topical therapies need further investigation as adjuncts or alternatives to surgical therapy for CIN 2/3.

The efficacy of topical imiquimod in high-grade cervical intraepithelial neoplasia: A systematic review and meta-analysis.

A major side effect of cervical excision for high-grade cervical intraepithelial neoplasia (CIN) is premature birth. A non-invasive treatment for reproductive age women is warranted. The aim of the present study was to determine the efficacy of topical imiquimod in the treatment of high-grade CIN, defined as a regression to ≤CIN 1, and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared with surgical treatment and placebo. Databases were searched for articles from their inception to February 2023.The study protocol number was INPLASY2022110046. Original studies reporting the efficacy of topical imiquimod in CIN 2, CIN 3 or persistent hr-HPV infections were included. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist. Five studies were included (n = 463). Histological regression to ≤CIN 1 was 55% in imiquimod versus 29% in placebo, and 93% in surgical treatment. Imiquimod-treated women had a greater odds of histological regression to ≤CIN 1 than placebo (odds ratio [OR] 4.17, 95% confidence interval [CI] 2.03-8.54). In comparison to imiquimod, surgical treatment had an OR of 14.81(95% CI 6.59-33.27) for histological regression to ≤CIN 1. The hr-HPV clearance rate was 53.4% after imiquimod and 66% after surgical treatment (95% CI 0.62-23.77). The histological regression rate is highest for surgical treatment followed by imiquimod treatment and placebo.

Carcinogenesis and management of human papillomavirus-associated cervical cancer.

Approximately 95% of cervical cancer are caused by human papillomavirus (HPV) infection. Although it is estimated that HPV-associated cervical cancer will decrease with the widespread use of HPV vaccine, it may take time for HPV-associated cervical cancer to be eliminated. For the appropriate management of HPV-associated cervical cancer, it is important to understand the detailed mechanisms of cervical cancer development. First, the cellular origin of most cervical cancers is thought to be cells in the squamocolumnar junction (SCJ) of the uterine cervix. Therefore, it is important to understand the characteristics of SCJ for cervical cancer screening and treatment. Second, cervical cancer is caused by high risk HPV (HR-HPV) infection, however, the manner of progression to cervical cancer differs depending on the type of HR-HPV: HPV16 is characterized by a stepwise carcinogenesis, HPV18 is difficult to detect in precancerous lesions, and HPV52, 58 tends to remain in the state of cervical intraepithelial neoplasia (CIN). Third, in addition to the type of HPV, the involvement of the human immune response is also important in the progression and regression of cervical cancer. In this review, we demonstrate the carcinogenesis mechanism of HPV-associated cervical cancer, management of CIN, and the current treatment of CIN and cervical cancer.

The 5-year risk of recurrence of grade 2/3 cervical intraepithelial neoplasia after treatment in a population screening programme by human papillomavirus status: A cohort study in central Italy.

(a) To estimate the risk of recurrent cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+), lesions within 5 years of follow-up in human papillomavirus-negative/human papillomavirus-positive cohorts; (b) to assess whether certain risk factors can predict the recurrence of CIN2+/CIN3+ lesions; and (c) to provide recommendations for follow-up after treatment of cervical intraepithelial neoplasia, grade 2/3 to prevent cervical cancer. Organized cervical cancer screening programme in Central Italy. We included 1063 consecutive first excisional treatments performed between 2006 and 2014 for screening-detected cervical intraepithelial neoplasia, grade 2/3 lesions among women aged 25-65. The study population was divided into two groups according to the human papillomavirus test results performed 6 months after treatment: Human papillomavirus-negative and human papillomavirus-positive cohorts. The 5-year risk of developing cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+) was estimated using the Kaplan-Meier method and the Cox regression model. Among 829 human papillomavirus-negative and 234 human papillomavirus-positive women, six (0.72%; three cervical intraepithelial neoplasia, grade 2, three cervical intraepithelial neoplasia, grade 3) and 45 (19.2%; 15 cervical intraepithelial neoplasia, grade 2, 30 cervical intraepithelial neoplasia, grade 3), respectively, developed CIN2+ recurrence within 5 years of follow-up. The cumulative risks for CIN2+ and CIN3+ were 0.9% (95% confidence interval: 0.4%-2.0%) and 0.5% (95% confidence interval: 0.1%-1.4%), respectively, for the human papillomavirus-negative cohort, and 24.8% (95% confidence interval: 18.5%-32.7%) and 16.9% (95% confidence interval: 11.4%-24.5%), respectively, for the human papillomavirus-positive cohort. Risk factors associated with increased risk of recurrence were both margins positive for the human papillomavirus-negative cohort, and positive margins, cervical intraepithelial neoplasia, grade 3 lesions, high-grade cytology and high viral load for the human papillomavirus-positive cohort. Human papillomavirus testing can identify women at increased risk of recurrence and this supports a recommendation for its use in the post-treatment follow-up of cervical intraepithelial neoplasia, grade 2/3 lesions.

The Effects of Dietary Nutrient Intake on Cervical Cancer: A Brief Review

AbstractCervical cancer (CC) results from a subsequent process, starting from the infection of normal cervical epithelium with oncogenic human papillomavirus and gradually progressing to cervical intraepithelial neoplasia (CIN), before finally developing into invasive cervical cancer (ICC). Over recent decades, dietary micronutrients have gained much attention due to their pivotal role in cancer prevention. We reviewed several relevant literature studies to investigate the protective roles of dietary nutrient intake in CC. Dietary intake of vitamin C, green–yellow vegetables, and provitamin A carotenoids that are rich sources of antioxidants may widely inhibit the process of CC development, whereas vitamins A and D might be more helpful in preventing the early events in the disease development. Vitamin E, lycopene, and folate are more effective for the treatment of high-grade CIN. Fruits exert their protective effects in the late stages of the cancer process, thus playing a vital role in ICC prevention. Polyphenols, flavonoids, and polyunsaturated fatty acids are more often used in cases of CC in combination with chemotherapy and radiotherapy. Thus, as a primary prevention strategy, the health benefits of various nutrients in CC must be clarified by vitro and in vivo approaches rather than epidemiological studies.